2) Follow this 🧵for your credit!
— @CKD_ce (@ckd_ce) June 14, 2023
Statement of accreditation and faculty disclosures are at https://t.co/PHlIppl6Yw. This program is intended for #healthcare #providers and is supported by an unrestricted educational grant from GSK.#FOAMed #nephtwitter @MedTweetorials
4) Let's start off with a POP 🍾QUIZ!
— @CKD_ce (@ckd_ce) June 14, 2023
Which of these #anemia treatments would expect to decrease #cardiovascular events and death in a new #hemodialysis patient?
A. Epoetin/Darbepoetin
B. A HIF-PHI
C. IV Iron
D. None
5b) . . . reduced #transfusions, major Cardiovascular events and death (#MACE), and did not increase infections. Here’s the primary outcome measure… pic.twitter.com/re4wC4ST79
— @CKD_ce (@ckd_ce) June 14, 2023
6) So the first lesson about #anemia management in #CKD for patients on dialysis is to establish & maintain adequate iron stores. This has been shown to reduce transfusions, reduce the need for Epoetin or other erythropoiesis-stimulating agents (#ESA), and reduce #MACE.
— @CKD_ce (@ckd_ce) June 14, 2023
7b) #ESAs have also shortened survival and/or increased risk of tumor progression in a number of cancer trials.
— @CKD_ce (@ckd_ce) June 14, 2023
(TTP=time to progression; H&N Ca=head & neck cancer; OS=overall survival) pic.twitter.com/tr8R6gYjG7
8b) These drugs stabilize #HIF, turning on several genes, including ones for erythropoietin #EPO and several iron-related transporters. BTW, earn more 🆓CE/#CME on this topic at https://t.co/1w968lFN0E with author @edgarvlermamd
— @CKD_ce (@ckd_ce) June 14, 2023
10a) Here’s an anemia correction trial in anemic patients with CKD-stage 3-5 not yet on dialysis.
— @CKD_ce (@ckd_ce) June 14, 2023
🔓 https://t.co/67tj8BOlda pic.twitter.com/SGS5jsqsjE
11a) And here is a trial in #dialysis patients already on #ESA and at Hb goal, randomized to #Daprodustat or an ESA. Again, both therapies maintained Hb in the desired range for up to 148 weeks.
— @CKD_ce (@ckd_ce) June 14, 2023
See 🔓 https://t.co/pkWbFrSxqF pic.twitter.com/OgRQkLnK5X
12a) But what about safety? #Roxadustat was the first HIF-PHI reviewed by @US_FDA & it was declined approval 2021. The primary #MACE endpoints in CKD-ND and dialysis trials were not significantly different . . .
— @CKD_ce (@ckd_ce) June 14, 2023
13) In August 2021, @US_FDA cited concerns about potential increased #thrombotic events and #MACE with #roxadustat in both #CKD-ND and CKD-#dialysis trials, and declined approval. Roxadustat is approved in multiple other countries 🇨🇳🇯🇵🇨🇱🇰🇷
— @CKD_ce (@ckd_ce) June 14, 2023
14b) Note increased #MACE events were seen in the non-US cohort of patients. These patients were targeted to higher Hb goal than the US patients. It is unknown if this played a role in higher MACE events.
— @CKD_ce (@ckd_ce) June 14, 2023
16a) In March 2022, @US_FDA declined to approve #vadadustat in CKD-ND or CKD-DD populations, citing failure to meet noninferiority in MACE in the CKD-ND population, and the increased risk of #thromboembolic events, driven by vascular access thrombosis in #dialysis patients.
— @CKD_ce (@ckd_ce) June 14, 2023
17) #Daprodustat was next in the #FDA docket. Its trial in #CKD–#Dialysis patients vs #ESA showed comparable #MACE safety (HR 0.93 (95% CI 0.81-1.07). An endpoint of MACE events or #thrombotic events was also similar between therapies.
— @CKD_ce (@ckd_ce) June 14, 2023
See 🔓 https://t.co/pkWbFrSxqF pic.twitter.com/Ho5a40SOhD
19a) #Daprodustat vs #darbepoetin in #CKD-ND patients also showed similar safety based on #MACE.
— @CKD_ce (@ckd_ce) June 14, 2023
See 🔓 https://t.co/67tj8BOlda pic.twitter.com/AwZefqV8hg
20) In 2023, the #FDA approved #daprodustat for use in #CKD patients on #dialysis 4 or more months. It was not approved for CKD-ND patients with #anemia “because its safety has not been established in that population.”
— @CKD_ce (@ckd_ce) June 14, 2023
22) While #daprodustat’s black box warning label doesn’t mention risk of cancer progression or recurrence, pts with active cancer were excluded from trials. Higher #HIF activity may play a role in some cancers. Lastly, the label recommends avoiding daprodustat if active #cancer. pic.twitter.com/nIT4uIihYT
— @CKD_ce (@ckd_ce) June 14, 2023
24) The #cardiovascular safety of HIF-PHIs appears similar to #ESA agents. Longer term monitoring of risks and benefits of patients on HIF-PHIs is warranted.
— @CKD_ce (@ckd_ce) June 14, 2023
25b) It's a, #CKD patients on #dialysis only. Here's a reminder of the key Phase 3 data that supported that indication: pic.twitter.com/prBTt1RWPA
— @CKD_ce (@ckd_ce) June 14, 2023
26) You just earned 0.5hr CE/#CME, #physicians #physicianassociates #nurses #NPs #pharmacists! Go to https://t.co/wiKc1fDq12 & grab your certificate. .@DrDanMO thanks you for JOINING us, invites you to FOLLOW us, and reminds you to watch the 📽️ at https://t.co/61lXmmrk5f.
— @CKD_ce (@ckd_ce) June 14, 2023